Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. FGFs are also known as heparin binding growth factors because they bind heparin and their ability to bind and activate their receptors is modulated by heparin. Suggestive of a paracrine effector, KGF is produced by cells of mesenchymal origin but is active primarily, if not exclusively on epithelial cells such as adult mammary epithelium, pancreatic ductal epithelium, and type II pneumocytes. KGF is involved in a variety of physiological and pathological processes including proliferation, differentiation, wound healing, cytoprotection, and inflammatory bowel disease. A systematic approach based on a prior study was used to elucidate the relationship between structure and function of KGF. The crystal structures of FGF-1 and FGF2 have been solved and it is most likely that all members of the FGF family have the same fold - a six stranded beta barrel atop three pairs of antiparallel beta hairpins with a three fold axis of symmetry about the axis of the barrel. Exploiting this symmetry, nine peptides that each span one third of KGF were synthesized. These peptides were then assayed for their ability to bind heparin, bind the receptor, and induce proliferation in keratinocytes. Our results implicate a single epitope on KGF important for both heparin binding and receptor binding.